The goal of this proposal is to determine the feasibility of optimizing polymeric tissue scaffolds using novel Surface Modifying Endgroups (SME). Biostable segmented polyurethane's (SPU) will be synthesized with five different SMEs and tested by in vitro cell culture. These surface-modified SPUs will include three 'passive' SMEs with decreasing hydrophobicity; fluorocarbon, silicone and polyethyleneoxide (PEO), an SME that binds heparin, and a PEO SME that covalently bind peptides. The base polymer will be Biospan SPU, a widely used cardiovascular biomaterial with a comprehensive FDA Master File. Surfaces will be characterized by Sum Frequency Generation (SFG) vibrational spectroscopy, Atomic Force Microscopy (AFM), and Contact Angle Goniometry. Tensile properties will be measured on an Instron. Phase I will determine cellular response to water-extracted films of the materials. In vitro studies will include: cell adhesion force, cell migration, cell proliferation, cell apoptosis, and cell differentiation. In Phase II, promising materials will be used to manufacture a small-diameter, microporous vascular graft for in vivo testing, using fabrication methods already developed by the PI for two existing clinical SPU vascular grafts. In Phase II SMEs will be coupled to a base polymer that biodegrades to liquid by-product: a novel family of polyethyleneoxide block copolymers with tailorable degradation rate.